The usefulness of serology against CagA of Helicobacter pylori as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear among several ethnic populations with a high prevalence of cagA-positive strains. We investigated ethnic differences of CagA serology in two sets of case-control subjects, Japanese-Brazilians (JB) and non-Japanese Brazilians (NJB). We performed a cross-sectional comparison of IgG antibody titers to CagA (CagA-Ab) and the combination of CagA-Ab with conventional surface antigen (Hp-Ab) in 80 JB and 178 NJB ncGC patients and their controls (160 JB and 178 NJB). The level of CagA-Ab titer in cancer cases was significantly higher in NJB than in JB. The strength of the association between CagA-Ab seropositivity (+) (> or = 10 U/ml) and ncGC was almost 2-fold higher in NJB than in JB [odds ratio (OR) (95% confidence interval), 4.5 (2.6-7.8) and 2.1 (1.2-3.6), respectively]. However, in both JB and NJB, the OR was highest in CagA-Ab(+) subjects with low titer (10-29 U/ml), and decreased inversely with elevating CagA-Ab titer. In addition, the serological status of CagA-Ab(+) and Hp-Ab(-) showed a similar close association with ncGC between JB and NJB [5.4 (1.9-15.3) and 5.4 (2.0-15.0), respectively]. These results suggest that although the roles of CagA in the carcinogenic process of ncGC might be different between JB and NJB, the CagA-Ab could be a useful marker for ncGC, independently of ethnicity, particularly in high-risk individuals with the serological status of CagA-Ab(+) with low IgG titer or combined with Hp-Ab(-).